Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo.

Hanna LA, Foreman RK, Tarasenko IA, Kessler DS, Labosky PA
Genes Dev. 2002 16 (20): 2650-61

PMID: 12381664 · PMCID: PMC187464 · DOI:10.1101/gad.1020502

Critical to our understanding of the developmental potential of stem cells and subsequent control of their differentiation in vitro and in vivo is a thorough understanding of the genes that control stem cell fate. Here, we report that Foxd3, a member of the forkhead family of transcriptional regulators, is required for maintenance of embryonic cells of the early mouse embryo. Foxd3-/- embryos die after implantation at approximately 6.5 days postcoitum with a loss of epiblast cells, expansion of proximal extraembryonic tissues, and a distal, mislocalized anterior organizing center. Moreover, it has not been possible to establish Foxd3-/- ES cell lines or to generate Foxd3-/- teratocarcinomas. Chimera analysis reveals that Foxd3 function is required in the epiblast and that Foxd3-/- embryos can be rescued by a small number of wild-type cells. Foxd3-/- mutant blastocysts appear morphologically normal and express Oct4, Sox2, and Fgf4, but when placed in vitro the inner cell mass initially proliferates and then fails to expand even when Fgf4 is added. These results establish Foxd3 as a factor required for the maintenance of progenitor cells in the mammalian embryo.

MeSH Terms (27)

Animals Blastocyst Cell Differentiation Cells, Cultured DNA-Binding Proteins DNA Primers Embryonic and Fetal Development Female Fibroblast Growth Factor 4 Fibroblast Growth Factors Forkhead Transcription Factors Gene Expression Regulation, Developmental Helix-Turn-Helix Motifs In Situ Hybridization In Vitro Techniques Male Mice Mice, Inbred C57BL Mice, Mutant Strains Octamer Transcription Factor-3 Pluripotent Stem Cells Proto-Oncogene Proteins Repressor Proteins Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Transcription Factors

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